Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line
Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line
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DOI：
10.1111/j.1471-4159.2009.06394.x
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发表时间：
2009-12-01
影响因子：
4.7
通讯作者：
Hrelia, Patrizia
中科院分区：
文献类型：
--
作者：
Tarozzi, Andrea;Morroni, Fabiana;Hrelia, Patrizia
在黑质（SN）中观察到的总GSH耗竭似乎是帕金森病患者随后氧化应激（OS）、线粒体功能障碍和多巴胺能细胞丢失的原因。预防SN中多巴胺能细胞OS的策略可能是使用化学预防剂作为内源性GSH、抗氧化剂和2相酶的诱导剂。在这项研究中，我们证明，治疗多巴胺能神经母细胞瘤SH-SY 5 Y细胞系萝卜硫素（SF），十字花科蔬菜诱导剂，导致总GSH水平显着增加，NAD（P）H：醌氧化还原酶-1，GSH-转移酶和还原酶，但没有GSH-过氧化物酶，过氧化氢酶和超氧化物歧化酶的活性。此外，GSH水平，GSH-转移酶和NAD（P）H：醌氧化还原酶-1活性的升高与SH-SY 5 Y细胞对H2 O2或6-羟基多巴胺（6-OHDA）诱导的毒性的抗性增加相关。用SF预处理SH-SY 5 Y细胞也显示出防止由6-OHDA引起的各种凋亡事件（线粒体去极化、半胱天冬酶9和3活化和DNA片段化）和坏死。此外，SF预处理有效地抵消了6-OHDA暴露后细胞内抗氧化能力和活性氧形成的损害。最后，SF的细胞保护和抗氧化作用被废除，另外丁硫氨酸亚砜亚胺支持的主要作用，谷胱甘肽在SF显示的神经保护作用。这些发现表明，SF可能在预防帕金森病方面发挥作用。
The total GSH depletion observed in the substantia nigra (SN) appears to be responsible for subsequent oxidative stress (OS), mitochondrial dysfunction, and dopaminergic cell loss in patients with Parkinson's disease. A strategy to prevent the OS of dopaminergic cells in the SN may be the use of chemopreventive agents as inducers of endogenous GSH, antioxidant and phase 2 enzymes. In this study, we demonstrated that treatment of the dopaminergic-like neuroblastoma SH-SY5Y cell line with sulforaphane (SF), a cruciferous vegetables inducer, resulted in significant increases of total GSH level, NAD(P)H : quinone oxidoreductase-1, GSH-transferase and -reductase, but not GSH-peroxidase, catalase and superoxide dismutase activities. Further, the elevation of GSH levels, GSH-transferase and NAD(P)H:quinone oxidoreductase-1 activities was correlated to an increase of the resistance of SH-SY5Y cells to toxicity induced by H2O2 or 6-hydroxydopamine (6-OHDA). The pre-treatment of SH-SY5Y cells with SF was also shown to prevent various apoptotic events (mitochondrial depolarization, caspase 9 and 3 activation and DNA fragmentation) and necrosis elicited by 6-OHDA. Further, the impairment of antioxidant capacity and reactive oxygen species formation at intracellular level after exposure to 6-OHDA was effectively counteracted by pre-treatment with SF. Last, both the cytoprotective and antioxidant effects of SF were abolished by the addition of buthionine sulfoximine supporting the main role of GSH in the neuroprotective effects displayed by SF. These findings show that SF may play a role in preventing Parkinson's disease.